Rodríguez Ces, Ana MaríaRapado González, ÓscarAguín Losada, SantiagoFormoso García, InésLópez Cedrún, José LuisTriana Martínez, GabrielLópez López, RafaelSuárez Cunqueiro, María Mercedes2025-09-152025-09-152025Rodríguez-Ces, A. M., Ó. Rapado-González, S. Aguín-Losada, et al. 2025. “ Circulating Cell-Free DNA Concentration as a Biomarker in Head and Neck Cancer.” Oral Diseases 1–12. https://doi.org/10.1111/odi.70002https://hdl.handle.net/10347/42819Objective Head and neck squamous cell carcinoma (HNSCC), particularly human papillomavirus (HPV) -negative HNSCC, poses a significant clinical challenge due to late diagnoses and poor survival. This study evaluates the potential of circulating cell-free DNA (ccfDNA) as a minimally invasive biomarker for diagnosis, prognosis and disease monitoring in HNSCC. Methods We conducted a multicentre, prospective study enrolling 85 patients across all disease stages and 28 healthy controls, using two quantification ccfDNA methods: fluorometry (Qubit) and quantitative real-time polymerase chain reaction (qPCR). Results Baseline plasma ccfDNA concentrations were significantly elevated in HNSCC patients compared to healthy controls, with an area under the curve of 0.705. Higher ccfDNA levels were observed in early-stage HNSCC patients. While ccfDNA levels correlated with age, no significant associations were found with tumour stage or location. Patients with lower post-treatment ccfDNA levels demonstrated longer median progression-free survival (PFS) (16.37 months vs. 9.63 months, p < 0.05). Longitudinal analysis of locally advanced HNSCC revealed significant inter-patient variability in ccfDNA kinetics. Conclusions Our study demonstrates the potential value of fluorometric ccfDNA quantification as a diagnostic, prognostic and monitoring biomarker for HNSCC. However, further well-designed studies must be carried out to enhance the clinical utility of ccfDNA as a biomarker for HNSCC management.eng© 2025 The Author(s). Oral Diseases published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are madeAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/BiomarkerCell-free DNADiagnosticHead and neck cancerQuantificationjournal article10.1111/odi.700021601-0825open access